IRBIS: a systematic search for conserved complementarity

Pervouchine, Dmitri D.

doi:10.1261/rna.045088.114

Cited by 17 publications

(39 citation statements)

References 59 publications

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“…In silico approaches such as comparative genomics and structural prediction are useful for identifying base-pairing interactions (Plocik and Graveley 2013); however, highly complex RNA interactions may be extremely difficult to predict (Cruz and Westhof 2009). The RNA bidirectional structural architectures identified in our study were not detected using recent high-throughput RNA structure sequencing techniques Li et al 2012), nor were they discovered by in silico approaches, although stem II of the Drosophila srp pre-mRNA was predicted Pervouchine 2014). Moreover, most RNA structural studies focus on the role of a local RNA duplex in alternative splicing and other processing.…”

Section: Discussionmentioning

confidence: 60%

Long-range RNA pairings contribute to mutually exclusive splicing

Yue

Yang

Dai

et al. 2015

RNA

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Mutually exclusive splicing is an important means of increasing the protein repertoire, by which the Down's syndrome cell adhesion molecule (Dscam) gene potentially generates 38,016 different isoforms in Drosophila melanogaster. However, the regulatory mechanisms remain obscure due to the complexity of the Dscam exon cluster. Here, we reveal a molecular model for the regulation of the mutually exclusive splicing of the serpent pre-mRNA based on competition between upstream and downstream RNA pairings. Such dual RNA pairings confer fine tuning of the inclusion of alternative exons. Moreover, we demonstrate that the splicing outcome of alternative exons is mediated in relative pairing strength-correlated mode. Combined comparative genomics analysis and experimental evidence revealed similar bidirectional structural architectures in exon clusters 4 and 9 of the Dscam gene. Our findings provide a novel mechanistic framework for the regulation of mutually exclusive splicing and may offer potentially applicable insights into long-range RNA-RNA interactions in gene regulatory networks.

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Section: Discussionmentioning

confidence: 60%

Long-range RNA pairings contribute to mutually exclusive splicing

Yue

Yang

Dai

et al. 2015

RNA

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“…from [23] ( Figure S2). The structure responsible for splicing of the intron between exons 9 and 10 in SF1 [33] was in group III (-25.1 kcal/mol); the structure associated with exon 46-52 skipping in DST [34] was in group II (−24.3 kcal/mol); a long-distance intronic interaction that regulates PLP1/DM20 splicing [37] was in group I (−15.8 kcal/mol); the structure that was suggested to regulate mutually exclusive exon choice in DNM1 [38] was in group III (−25.9 kcal/mol). The RNA bridge in ENAH [39] also belongs to group I (−19.4 kcal/mol) and spreads over 1,700 nts, indicating that less stable RNA structures are not less functional or less interesting than the others.…”

Section: Rna Structures Listed Inmentioning

confidence: 99%

“…Computational identification of long-range RNA structure therefore remains a great challenge in RNA biology.Comparative genomics provides a powerful alternative to de novo RNA folding by detecting signatures of evolutionary covariation [31,32]. In previous reports, we presented a methodology that implemented simultaneous alignment and RNA folding using k-mers [28,33,34]. However, in the vast majority of cases, sequence alignments have insufficient variation to detect covariations [34].…”

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confidence: 99%

“…In previous reports, we presented a methodology that implemented simultaneous alignment and RNA folding using k-mers [28,33,34]. However, in the vast majority of cases, sequence alignments have insufficient variation to detect covariations [34]. This motivated us to revisit this question, this time with a much simpler approach that finds pairs of conserved complementary regions (PCCR) in pre-aligned evolutionarily-conserved regions.…”

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confidence: 99%

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Conserved long-range base pairings are associated with pre-mRNA processing of human genes

Kalmykova

Kalinina

Denisov

et al. 2020

Preprint

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The ability of nucleic acids to form double-stranded structures is essential for all living systems on Earth. While DNA employs it for genome replication, RNA molecules fold into complicated secondary and tertiary structures. Current knowledge on functional RNA structures in human protein-coding genes is focused on locally-occurring base pairs. However, chemical crosslinking and proximity ligation experiments have demonstrated that long-range RNA structures are highly abundant. Here, we present the most complete to-date catalog of conserved long-range RNA structures in the human transcriptome, which consists of 1.1 million pairs of conserved complementary regions (PCCRs). PCCRs tend to occur within introns proximally to splice sites, suppress intervening exons, circumscribe circular RNAs, and exert an obstructive effect on cryptic and inactive splice sites. The double-stranded structure of PCCRs is supported by a significant decrease of icSHAPE nucleotide accessibility, high abundance of A-to-I RNA editing sites, and frequent nearby occurrence of forked eCLIP peaks. Introns with PCCRs show a distinct splicing pattern in response to RNA Pol II slowdown suggesting that splicing is widely affected by co-transcriptional RNA folding. Additionally, transcript starts and ends are strongly enriched in regions between complementary parts of PCCRs, leading to an intriguing hypothesis that RNA folding coupled with splicing could mediate co-transcriptional suppression of premature cleavage and polyadenylation events. PCCR detection procedure is highly sensitive with respect to bona fide validated RNA structures at the expense of having a high false positive rate, which cannot be reduced without loss of sensitivity.The catalog of PCCRs is visualized through a UCSC Genome Browser track hub to facilitate further genome research on long-range RNA structures.Double-stranded structure is a key feature of nucleic acids that enables replicating the genomic information and underlies fundamental cellular processes [1,2]. Many RNAs adopt functional secondary structures, and mRNAs are no exception although their main role is to encode proteins [3,4,5,6]. In eukaryotes, RNA structure affects gene expression through modulating all steps of pre-mRNA processing including splicing [7], cleavage and polyadenylation [8], and RNA editing [9]. The loss of functional RNA structure has been increasingly reported as implicated in hereditary disease and cancer [10,11,12,13].Recent progress in high-throughput sequencing techniques enabled several experimental strategies to determine RNA structure in vivo [14,15,16]. Chemical RNA structure probing can reveal which bases are single-or double-stranded, but it cannot determine which nucleotides form base pairs [17,18,19,20,21].In order to identify the interacting partners, RNA structure probing has to be combined with de novo RNA structure prediction [22], but due to a number of technical limitations such methods cannot account for base pairings that are far apart [23]. Photo-inducible RNA crosslinking a...

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“…Andronescu et al [29] developed the PairFold algorithm for secondary structure prediction of minimum free energy. Pervouchine [30], Alkan et al [31] and Kato et al [32] presented different dynamic programming algorithms with different scoring functions for predicting secondary structures, respectively. However, these algorithms cannot deal with circular single-stranded DNA tiles.…”

Section: Introductionmentioning

confidence: 99%

A Dynamic Programming Algorithm for Circular Single-stranded DNA Tiles Secondary Structure Prediction

Zhang¹,

Huang²,

Xiaolong³

et al. 2013

Appl. Math. Inf. Sci.

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Abstract:The design of DNA sequences is critical for many research fields such as DNA self-assembly, DNA hybridization arrays, DNA computing, and PCR-based applications. DNA secondary structure prediction is the key part for these DNA nanotechnologies. In this paper, we present a dynamic programming algorithm to predict the secondary structure of single-stranded DNA tiles. The algorithm calculates all possible maximum matches based on the nearest-neighbour model and global energy minimization. Experimental results show that the algorithm performers significantly to predict secondary structures for single-stranded DNA tiles.

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IRBIS: a systematic search for conserved complementarity

Cited by 17 publications

References 59 publications

Long-range RNA pairings contribute to mutually exclusive splicing

Long-range RNA pairings contribute to mutually exclusive splicing

Conserved long-range base pairings are associated with pre-mRNA processing of human genes

A Dynamic Programming Algorithm for Circular Single-stranded DNA Tiles Secondary Structure Prediction

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